Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan

Mol Ther. 2021 Jul 7;29(7):2366-2377. doi: 10.1016/j.ymthe.2021.03.020. Epub 2021 Mar 27.


Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a ( NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6-180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway.

Keywords: ChAd63-KH vaccine; PKDL; Sudan; clinical trial; immunogenicity; leishmaniasis; safety; transcriptomics.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Simian / genetics
  • Adolescent
  • Adult
  • Antigens, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Child
  • Female
  • Humans
  • Injections, Intramuscular
  • Leishmania / immunology*
  • Leishmania / isolation & purification
  • Leishmaniasis Vaccines / administration & dosage*
  • Leishmaniasis Vaccines / immunology
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / prevention & control*
  • Male
  • Prognosis
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / immunology
  • Young Adult


  • Antigens, Protozoan
  • Leishmaniasis Vaccines
  • Vaccines, Synthetic

Associated data